Microorganisms are widely used for industrially producing a broad range of useful substances, including alcoholic beverages, certain types of foods such as bean paste (miso) and soy sauce (shoyu), amino acids, organic acids, nucleic-acid-related substances, antibiotics, carbohydrates, lipids, and proteins. Also, these substances are used in a variety of fields, including foods, pharmaceuticals, detergents, products for daily use such as cosmetics, and various chemical raw materials.
In industrial production of useful substances by means of microorganisms, improvement of productivity is one major topic of interest, and one approach therefor is breeding of microorganisms through mutagenesis or other genetic techniques. Recently, in particular, with advancement of microbial genetics and biotechnology, more effective breeding of useful microorganisms has been performed through genetic recombination or other techniques.
In addition, in association with recent rapid development of genome analysis techniques, attempts have been made to actively apply the genomic information of microorganisms of interest to industrial uses. Industrially useful host microorganisms whose genomic information has been disclosed include Bacillus subtilis Marburg No. 168 (Non-Patent Document 1), Escherichia coli K-12 MG1655 (Non-Patent Document 2), and Corynebacterium glutamicum ATCC132032. Such microorganisms have been improved on the basis of the disclosed genomic information.
However, despite the aforementioned attempts, their efficiency of producing useful substances has not necessarily been satisfactory.
A prsA gene has been found as a gene involved in a protein secretion process in Bacillus subtilis, and hitherto conducted studies have suggested that PrsA has a chaperone-like function of facilitating folding of the protein transported to the outside of the cytoplasm through the cell membrane. Meanwhile, there has been reported a microorganism in which productivity of a protein of interest is improved by introducing therein a plasmid in which a Bacillus subtilis prsA gene including the promoter region of the gene has been inserted, so that the microorganism has a plurality of prsA genes (Non-Patent Document 3).
However, this microorganism poses practical difficulties because the number of plasmids introduced into one cell is difficult to be controlled, and removal of plasmids often occurs during culturing the microorganism.
As has also been reported, a cloning vector pHP13 in which a prsA gene fragment has been inserted exhibits a function of replicating a Bacillus subtilis plasmid pTA1060 (Non-Patent Document 4), and the average number of pTA1060 copies for one Bacillus subtilis genome, i.e. one Bacillus subtilis cell, is 5.2 (Non-Patent Document 5).
Since the amount of a protein of interest produced by the above-reported microorganism is 1 to 5 times that produced by a wild-type strain, the amount of a protein of interest produced per introduced prsA gene is about 0.2 to about 1 times that produced by the wild-type strain. Therefore, satisfactory effects are not obtained through introduction of the prsA gene.
As has been reported, in Bacillus subtilis, the abrB gene encodes a transcription factor which plays an important role in controlling expression of various genes involved in, for example, sporulation, competence, or nutrition acquisition during the transition from logarithmic growth phase to stationary phase (Non-Patent Documents 6 and 7).
As has been known, dltA, dltB, dltC, dltD, and dltE genes belong to the same operon, and these genes are involved in addition of D-alanine to teichoic acid present in the cell wall and the cell membrane. As has also been reported, protein secretion is improved through inhibition of the functions of these genes (Non-Patent Documents 8 to 10).
However, there has not yet been known a microorganism which overexpresses a prsA gene, and in which an abrB gene, a dltA gene, a dltB gene, a dltC gene, a dltD gene, or a dltE gene is inactivated. In addition, such a microorganism is not even expected to exhibit excellent productivity of a useful protein or polypeptide as compared with a microorganism which overexpresses a prsA gene.    Non-Patent Document 1: Nature, 390, 249, 1997    Non-Patent Document 2: Science, 277, 1453, 1997    Non-Patent Document 3: Mol. Microbiol., 8: 727 (1993)    Non-Patent Document 4: Mol. Gen. Genet., 209: 335 (1987)    Non-Patent Document 5: Plasmid, 18: 8 (1987)    Non-Patent Document 6: Mol. Microbiol., 7: 337 (1993)    Non-Patent Document 7: Cell Mol. Life. Sci., 59: 392 (2002)    Non-Patent Document 8: J. Biol. Chem., 270: 15598 (1995)    Non-Patent Document 9: Microbiology, 145: 3409 (1999)    Non-Patent Document 10: Appl. Environ. Microbiol., 68: 227 (2002)